Risk of second brain tumour after conservative surgery and radiotherapy for pituitary adenoma.

OBJECTIVE--To assess the risk of second brain tumour in patients with pituitary adenoma treated with conservative surgery and external beam radiotherapy. DESIGN--Long term follow up of a cohort of patients with pituitary adenoma and comparison of tumour occurrence with population incidence rates. SETTING--The Royal Marsden Hospital. SUBJECTS--334 patients with pituitary adenoma treated with conservative surgery and radiotherapy (median dose 45 Gy) and followed up for 3760 person years. MAIN OUTCOME MEASURES--Second intracranial tumour and systemic malignancy. RESULTS--Five patients developed a second brain tumour: two had astrocytoma, two meningioma, and one meningeal sarcoma. The cumulative risk of developing a second brain tumour over the first 10 years after treatment was 1.3% (95% confidence interval 0.4% to 3.9%) and over 20 years 1.9% (0.7% to 5.0%). The relative risk of a second brain tumour compared with the incidence in the normal population was 9.38 (3.05 to 21.89). There was no excess risk of any other type of second primary malignancy. CONCLUSIONS--There is an increased risk of second intracranial tumour in patients with pituitary adenoma treated with surgery and radiotherapy. Although radiation is likely to be the most important factor contributing to the excess risk, further study is required in a cohort of similar patients not receiving radiation.     

Natural History and Treatment of Wilms's Tumour: An Analysis of 335 Cases Occurring in England and Wales 1962-6

Hospital records and other data relating to Wilms''s tumour were analysed to elucidate both thenatural history of the disease and the effects of treatment, with special reference to actinomycin D. The age of maximum incidence was about 18 months; left-sided tumours were significantly more common than right-sided ones.Prognosis was related to stage of the disease at the initial operation and to the occurrence of metastasis. The three-year survival rate for cases having a nephrectomy was 35%; no child who did not have a nephrectomy survived.Recurrence of the tumour was observed in two-thirds of the cases, almost always within two years of the initial treatment, irrespective of the child''s age. The three-year survival rate for this group was 11%.The effects of radiotherapy and chemotherapy are considered in detail. Very little improvement in survival rate could be ascribed to actinomycin D. The reasons for this and for the variations found in earlier reports on selected cases are possibly the addition of other components of treatment and differences in drug regimens. The findings suggest the need for controlled clinical trials.     

Prognostic factors in renal cell carcinoma

We studied 569 cases of renal cell carcinoma in the files of the Department of Pathology of the Norwegian Radium Hospital from 1964 to 1974. A nephrectomy had been performed in all cases. Clinical information on sex, age, survival time and metastases was traced. The histological slides were examined and tumour growth pattern, cell type, cell shape, nuclear atypia, abnormal nucleoli, nuclear grade, vascular invasion and tumour demarcation were all evaluated. Besides well-known prognostic factors such as tumour stage, presence or absence of metastases and vascular invasion, nuclear grade was found to be a useful prognostic factor. Younger patients were found to do better than older, and women better than men. Smaller tumours carried a better prognosis than larger and clear cell tumours had a better prognosis than those composed of eosinophilic or basophilic cells. The presence of spindle cells was a bad prognostic omen.     

Vascular endothelial growth factor A is a potential prognostic biomarker and correlates with immune cell infiltration in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related deaths among cancer patients. Vascular endothelial growth factor A (VEGFA) is involved in regulating biological processes, such as angiogenesis and vascular permeability, and is very closely related to the pathogenesis of various tumours, especially vascular-rich, solid tumours. Clinical data of patients with HCC and other tumours were analysed through public databases, such as the TCGA database, Gene Expression Omnibus database, Human Protein Atlas database, STRING, Tumour Immune Estimation Resource and Kaplan–Meier Plotter. The tumour tissues and adjacent normal tissues of patients with HCC from Hunan Provincial People's Hospital were collected to verify the expression of VEGFA by immunohistochemistry, immunofluorescence, Western blotting and qPCR. VEGFA expression is elevated in multiple tumour types and correlates with the prognosis of tumour patients. VEGFA is involved in regulating the tumour microenvironment and immune cell function in tumour development. Inhibition of VEGFA reduces proliferation, invasion, and migration and promotes apoptosis in HCC cells. VEGFA is a potential predictive biomarker for the diagnosis and prognosis of HCC.     

Signet ring cells in fine needle aspiration cytology of breast carcinomas: review of the cytological findings in ten cases identified by histology

Objective:  To establish whether the presence of signet ring cells (SRCs) in histology sections of breast carcinoma cases was reflected by their presence in fine needle aspiration cytology (FNAC) smears, correlating to the histological type of breast carcinoma.
Methods:  We reviewed the FNAC findings of ten cases that had been diagnosed as primary breast carcinoma with SRCs on histological sections between 1998 and 2007. Slides and histological sections were obtained from the archives of Ege University Hospital.
Results:  FNA smears were reviewed for the following cytomorphological features: background, cellularity, architecture, nuclear pleomorphism and the presence of SRCs. The background was bloody in eight cases, necrotic in one, and clean in one. There was no mucinous material in any of the cases. Cellularity was prominent in five cases (hypercellular), moderate in three (cellular) and low in two (hypocellular). Loosely cohesive groups of tumour cells of varying size were observed in all cases. A plasmacytoid appearance to some of the tumour cells was seen in all cases and discohesive tumour cells were present in eight. Nuclear pleomorphism was high in six cases and moderate in four. SRCs were observed in seven of the ten cases. Two of these seven cases also had a tubular pattern and one had tumour giant cells.
Conclusions:  FNAC should be evaluated carefully regarding the presence of SRCs when cells with a plasmacytoid appearance are observed in either hyper- or hypocellular smears. The presence of single SRCs in FNACs with hypercellularity, high nuclear grade and tubular formation or tumour giant cells may be a clue in favour of ductal carcinoma. The presence of single SRCs in FNACs with hypocellularity and mild to moderate nuclear grade may be suggestive of lobular carcinoma. However, larger studies would be needed to establish the predictive value of the presence of SRCs on FNAC.     

Does chronomodulated radiotherapy improve pathological response in locally advanced rectal cancer?

The predominant mode of radiation-induced cell death for solid tumours is mitotic catastrophe, which is in part dependent on sublethal damage repair being complete at around 6 h. Circadian variation appears to play a role in normal cellular division, and this could influence tumour response of radiation treatment depending on the time of treatment delivery. We tested the hypothesis that radiation treatment later in the day may improve tumour response and nodal downstaging in rectal cancer patients treated neoadjuvantly with radiation therapy. Recruitment was by retrospective review of 267 rectal cancer patients treated neoadjuvantly in the Department of Radiation Oncology at the Canberra Hospital between January 2010 and November 2015. One hundred and fifty-five patients met the inclusion criteria for which demographic, pathological and imaging data were collected, as well as the time of day patients received treatment with each fraction of radiotherapy. Data analysis was performed using the Statistical Package R with nonparametric methods of significance for all tests set at p < 0.05. Of the 45 female and 110 male patients, the median age was 64. Seventy-three percent had cT3 disease and there was a mean tumour distance from the anal verge of 7 cm. Time to surgical resection following radiotherapy ranged from 4 to 162 days with a median of 50 days, with a complete pathological response seen in 21% of patients. Patients exhibiting a favourable pathological response had smaller median pre- and postradiotherapy tumour size and had a greater change in tumour size following treatment (p < 0.01). Patients who received the majority of their radiotherapy fractions after 12:00 pm were more likely to show a complete or moderate pathological response (p = 0.035) and improved nodal downstaging. There were also more favourable responses amongst patients with longer time to surgical resection postradiotherapy (p < 0.004), although no relationship was seen between response and tumour distance from the anal verge. Females were less likely to exhibit several of the above responses. Neoadjuvant radiotherapy for locally advanced rectal cancer performed later in the day coupled with a longer time period to surgical resection may improve pathological tumour response rates and nodal downstaging. A prospective study in chronomodulated radiotherapy in this disease is warranted.     

Fine Needle Aspiration Cytology of the Breast: Factors Affecting Sensitivity

At Northampton General Hospital a pathologist takes, stains and immediately reports aspirates at a fine needle aspiration clinic which is run in conjunction with a busy surgical breast clinic. the effect of various factors on the sensitivity of the technique have been quantified. Small tumour size, certain types of tumour and lesions difficult to palpate are causes of reduced sensitivity. Acellular samples had little effect on sensitivity. In this clinic trainee aspirators achieved good results early in their experience. After one year each had improved to the level of an experienced aspirator.     

Comparative diagnostic efficacy of serum squamous cell carcinoma antigen in hepatocellular carcinoma

ABSTRACT: Hepatocellular carcinoma (HCC) is a common liver malignancy in Nigeria. Hepatitis B and C viruses, alcohol and Aflatoxin B are among the various aetiology. More work needs to be done in the search for markers that will aid early detection of this condition as it is uniformly fatal once advanced. Alphafetoprotein (AFP) remains the most widely used tumour marker of HCC detection in spite of its known shortcomings. The objective of this study was to determine the efficacy of serum squamous cell carcinoma antigen (SCCA) , in comparison to alphafetoprotein in the detection of HCC. METHOD: Sixty patients with HCC and thirty apparently healthy controls attending the Medical Outpatient Department(MOPD) of the University College Hospital Ibadan(UCH) Nigeria were selected for the study. Questionnaire was used to collect clinical data while AFP, SCCA levels,serum HBsAg and anti-HCV were determined using ELISA method- ( Diagnostic Automation Inc. Canada),Abdominal ultrasound scan was also done. Result:Thirty one(51.7%) out of 60 selected cases were positive for HBsAg while six(20%) out of 30 controls were positive for HBsAg(p= 0.004) .Out of the 60 cases selected for this study only 2 (3.3.%) cases were positive for hepatitis C virus, while only 1(3.3%) out of 30 control was positive for hepatitis C virus(p= 0.74). The mean AFP value for cases with HCC was 393.21ng/ml +/-386.97 compared to the control group which was 5.60 +/- 13.03 ng/ml (P value 0.001).The mean SCCA level was 0.64 +/- 0.56ng/ml and 0.71+/-0.65ng/ml for cases and controls respectively (p=0.631) CONCLUSION: Alphafetoprotein remains a good tumour marker for the diagnosis of HCC. Serum squamous cell carcinoma antigen(SCCA) has no discriminatory power and may not be useful as a tumour marker for Nigerians with hepatocellular carcinoma.     

Meningeal Carcinomatosis

Meningeal carcinomatosis without gross tumour in the substance of the brain or spinal cord has been reported rarely. Two cases observed at the Victoria General Hospital, Halifax, presented a bizarre clinical picture consisting of signs of meningeal irritation without fever, and psychotic behaviour. Examination of the cerebrospinal fluid revealed low sugar concentration and increased pressure, protein and cells. In one case these cells were readily identified as malignant on stained smears. At autopsy the surfaces of the cerebral hemispheres, cerebellum and brain stem were covered by an opalescent film and on section the subarachnoid space was densely packed with malignant cells. Both primary tumours were adenocarcinomas, one originating in the gallbladder and one in the rectum. The diagnosis of meningeal carcinomatosis must be considered in patients presenting with profound mental changes and meningeal irritation without fever. Diagnosis may be confirmed by cytological examination of the cerebrospinal fluid. The primary tumour is most commonly an adenocarcinoma. There is no satisfactory treatment available.     

Inpatient admissions and outpatient appointments in the first year post cancer diagnosis: A population based study from England

BackgroundTime spent in hospital (length of stay) is an important component of patient experience and the financial cost of cancer care. This study documents the length of stay across English cancer diagnoses at a national level and reports on variation by patient demographics and tumour characteristics.MethodsData on all diagnoses of malignant neoplasms from the English National Cancer Registration and Analysis Service for 252,202 patients first diagnosed in 2015 was linked with NHS Digital’s Admitted Patient Care and Outpatient Hospital Episode Statistics datasets to quantify length of stay within one year following diagnosis. Length of stay was modelled using linear regression adjusted for sex, age, tumour type, stage, time spent alive during the study period, vital status at end of study period, region, deprivation and ethnicity.ResultsPatients spend a mean of 25 days (median = 17 days; IQR = 8–34 days) in hospital in their first year. Tumour type, stage, age and vital status corrections had the strongest effects in the model adjusting for other independent variables. Younger patients tended towards longer stays.ConclusionLength of stay varies among patients by tumour type, age and stage. Estimating future health service demands should account for changes in incident tumour characteristics.     

Analysis of DNA adducts by accelerator mass spectrometry in human breast tissue after administration of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and benzo[a]pyrene

Epidemiological evidence has suggested an association between meat consumption and the risk of breast cancer. 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a heterocyclic amine found in cooked meat, has been implicated in the aetiology of breast cancer and has been shown to induce tumour formation in rodent mammary glands. In addition, polycyclic aromatic hydrocarbons, such as benzo[a]pyrene (B[a]P) which has also been shown to induce tumour formation at a number of sites in rodents including the breast, are produced during the cooking of meat through the pyrolysis of fats. The aim of this study was to examine the bioavailability of these compounds to human breast tissue and their ability to bind to DNA to form DNA adducts. Patients undergoing breast surgery at York District Hospital were orally administered prior to surgery a capsule containing 20microg of 14C PhIP (182kBq, specific activity 2.05GBq/mmol) or 5microg of 14C B[a]P (36kBq, specific activity 1.81GBq/mmol). At surgery, normal and tumour breast tissue was resected and tissue concentrations of carcinogen measured by liquid scintillation counting and DNA adduct levels by accelerator mass spectrometry (AMS) were subsequently determined. It was found that both 14C PhIP and 14C B[a]P were able to reach the target organ where they had the ability to form DNA adducts. The level of adducts ranged from 26.22-477.35 and 6.61-208. 38 adducts/10(12) nucleotides following administration of 14C PhIP and 14C B[a]P, respectively, with no significant difference observed between levels in normal or tumour tissue. In addition, the data obtained in this study were comparable to adduct levels previously found in colon samples following administration of the same compounds to individuals undergoing colorectal surgery. This is the first report that these two carcinogens bind to human breast DNA after administration of a defined low dose.     

Women with large breasts are at an increased risk of advanced breast cancer

Background

The risk of nodal metastasis is higher in women with bigger breast. It is not clear if this increase is due to the size of the breast (largely related to obesity) or is the result of larger tumour size at presentation (due to delayed diagnosis). It is hypothesised that women with large breasts are more likely to have node positive disease mainly attributable to their breast size.

Patients and methods

One hundred and twenty consecutive patients who underwent mastectomy during the year 2004 and 2005 for primary breast cancers in a large Teaching Hospital were included in the study. Patient's variable and tumour variable were collected and analysed by SPSS^® computer programme.

Results

It was found that big breasted women (those patients with mastectomy weight greater than 800 g) had a significantly greater tumour size than those with smaller breasts (p = 0.019, Mann-Whitney test) but there was no significant difference in grade (Kendall's tau-b = 0.055, p = 0.57) or lymph node positivity (Kendall's tau-b = 0.011, p = 0.93) between the two groups. Although, the tumour size was significantly greater in those with lymph node metastases (p < 0.001) but mastectomy weight was not found to be significantly greater in those with lymph node metastases (p = 0.11). For patients with similar tumour sizes mastectomy weight was not significantly greater in those patients with lymph node metastases (p = 0.28).

Conclusion

It is concluded that increased incidence of lymph node positivity at presentation big-breasted women is because of larger size of the primary tumour and not due to the size of the breast alone.

     

High energy neutron treatment for pelvic cancers: study stopped because of increased mortality.

OBJECTIVE--To compare high energy fast neutron treatment with conventional megavoltage x ray treatment in the management of locally advanced pelvic carcinomas (of the cervix, bladder, prostate, and rectum). DESIGN--Randomised study from February 1986; randomisation to neutron treatment or photon treatment was unstratified and in the ratio of 3 to 1 until January 1988, when randomisation was in the ratio 1 to 1 and stratified by site of tumour. SETTING--Mersey regional radiotherapy centre at Clatterbridge Hospital, Wirral. PATIENTS--151 patients with locally advanced, non-metastatic pelvic cancer (27 cervical, 69 of the bladder, seven prostatic, and 48 of the rectum). INTERVENTION--Randomisation to neutron treatment was stopped in February 1990. MAIN OUTCOME MEASURES--Patient survival and causes of death in relation to the development of metastatic disease and treatment related morbidity. RESULTS--In the first phase of the trial 42 patients were randomised to neutron treatment and 14 to photon treatment, and in the second phase 48 to neutron treatment and 47 to photon treatment. The relative risk of mortality for photons compared with neutrons was 0.66 (95% confidence interval 0.40 to 1.10) after adjustment for site of tumour and other important prognostic factors. Short term and long term complications were similar in both groups. CONCLUSIONS--The trial was stopped because of the increased mortality in patients with cancer of the cervix, bladder, or rectum treated with neutrons.     

Occult Carcinoma of the Bronchus

The term “occult carcinoma” is applied to those patients with carcinoma of the bronchus at an in situ or early invasive stage who have carcinoma cells in their sputum but have no recognizable evidence of tumour in the chest radiograph. In eight such patients at the Toronto General Hospital, the lesion was localized and treatment instituted. Our experience with these eight patients can be compared with that of 27 patients described in two similar studies. The lesions were commonly symptomatic. Localization, although sometimes difficult, was accomplished using information obtained during bronchoscopy and bronchography. The prognosis following adequate resection appeared excellent. No patient died of carcinoma during the post-treatment follow-up period, which was continued for a minimum of 18 months. Pathological evidence indicates that bronchial carcinoma at this occult stage can be diagnosed cytologically, is rarely multifocal and, as a localized neoplasm, is amenable to curative therapy.     

Amenorrhoea after Discontinuing Combined Oestrogen-Progestogen Oral Contraceptives

Out of 210 women seen at the Middlesex Hospital with secondary amenorrhoea the 63 who developed it after stopping oral contraceptives were fully investigated. Five had organic disease sufficient to account for the amenorrhoea (one had severe diabetes, one a pituitary tumour, and three premature ovarian failure); two patients had galactorrhoea (one of whom also had the pituitary tumour); two had anorexia nervosa.Of the 63 women 40 (63%) had suffered from amenorrhoea or prolonged or irregular menstrual cycles before taking the pill, and this suggested that combined oestrogen-progestogen oral contraceptives should be used with caution for women with irregular menstruation.Nineteen patients wished to become pregnant and 12 have so far done so after treatment with clomiphene or gonadotrophins.In another study 204 women recorded when their first menstrual cycle occurred after stopping the pill. Seventy-four had a cycle longer than five weeks but only five exceeded three months, and only one of the five had more than six months'' amenorrhoea. These results confirm that the incidence of amenorrhoea after stopping oral contraceptives is low.     

Primary Tumours of the Small Bowel and its Mesentery

Twenty-seven primary small bowel tumours encountered at the University of Alberta Hospital in a 10-year period have been reviewed. Seventeen symptomatic growths were treated by resection and 10 asymptomatic tumours were discovered incidentally. During this same period, three intramesenteric lipomas were found. Small bowel tumours were malignant in 15 of the 17 symptomatic cases and benign in seven of the nine asymptomatic cases. Carcinoid tumours, malignant lymphomas, non-lymphoid sarcomas and carcinomas were the common malignant neoplasms while adenomas, lipomas, myomas, fibromas and angiomas comprised the majority of benign growths reported. Symptoms of anorexia, anemia, abdominal pain, obstruction and hemorrhage suggest small bowel tumour if commoner pathology has been ruled out.     

Extramedullary plasmacytoma, a report of five cases diagnosed by FNAC

Objective:  To review cytological findings and diagnostic challenges in the use of fine needle aspiration in the diagnosis of extramedullary plasmacytoma.
Methods:  Five cases of extramedullary plasmacytoma that were initially diagnosed on fine needle aspiration cytology over a period of two years in Sir Ganga Ram Hospital were reviewed.
Results:  The cytological findings were similar in all five cases. The smears were cellular and composed of plasmacytoid cells arranged singly and in clusters, with varying pleomorphism, bi- and multinucleation and mitotic figures. Presence of anaplasia, increased plasmablasts, numerous naked nuclei and unusual location of the tumour were some of the challenges faced during the cytological evaluation.
Conclusions:  Extramedullary plasmacytoma may occur either as an initial presentation or as a secondary involvement by multiple myeloma. Fine needle aspiration is a reliable technique for its rapid diagnosis.     

Induction of VX2 carcinoma in rabbit liver: comparison of two inoculation methods

Direct injection of VX2 cell suspension into the liver is simple and widely used. Implantation of a fragment of VX2 tumour into the liver using a surgical technique has also been developed in the last decade. In this study, we compared these two methods in order to find a better modality for establishing VX2 liver mass. Forty rabbits, each weighing 2.8-3.2 kg, were divided into two groups, 20 rabbits in each. In Group 1, a tumour cell suspension containing 1 x 10(6) cells in a volume of 0.1 ml, was injected slowly into the liver parenchyma using a 27-gauge needle during laparotomy. In Group 2, a 1 mm(3) fragment of VX2 carcinoma was inoculated into the sub-capsule of the left anterior lobe of the liver. In Group 1, three rabbits showed no tumour growth and 10 rabbits showed evidence of leakage and tumour seeding outside of the liver. In Group 2, all but one rabbit showed tumour growth and none showed evidence of tumour seeding. The leakage rates were 50% and 0% for Group 1 and Group 2, respectively. Overall, the success inoculation rate was 35% for Group 1 and 95% for Group 2. In conclusion, to create the VX2 liver tumour model in rabbits, direct implantation of VX2 tumour fragment into the liver achieved better results than injecting cell suspension of VX2 tumour into the liver.     

In search of specific cytotoxic T lymphocytes infiltrating or accompanying human ovarian carcinoma

Summary Lymphocytes infiltrating human ovarian carcinoma obtained directly from the tumour mass (tumour-infiltrating lymphocytes, TIL) or from the carcinomatous ascites (tumour-associated lymphocytes, TAL) were expanded in vitro in long-term cultures with interleukin-2 and tested for their specific cytolytic activity. Killing of the autologous tumour was detected only in a proportion of the patients, less frequently in TIL compared to TAL. In fact two out of ten TIL and four out of nine TAL cultures tested showed significant levels of lysis against the autologous tumour. This cytotoxic activity was not restricted to the autologous tumour, as other tumour cell lines, including non-ovarian ones, were lysed as well. The cultures that were not cytotoxic against the autologous tumour were in most cases able to lyse other tumour cell lines of ovarian or other histology. Cloning of TIL from one patient was performed: of 22 clones tested, 4 displayed higher cytotoxicity against the autologous tumour compared to the uncloned population and 3 out of these 4 did not kill an irrelevant carcinoma cell line. In order to stimulate the expansion of putative specific effectors we performed mixed lymphocyte/tumour cultures (MLTC) with autologous or allogeneic tumour cells. No stimulation of cytotoxicity against the autologous tumour was detected after MLTC in nine different TAL populations, using autologous or allogeneic tumours as stimulators. On the contrary, peripheral blood lymphocytes from two patients after MLTC with the autologous tumour showed increased killing of the autologous and decreased killing of an allogeneic target. In conclusion TIL and TAL from ovarian carcinoma expanded in vitro with interleukin-2 usually have non-MHC-restricted cytotoxicity and variable degrees of reactivity against the autologous tumour. A preferential killing for the autologous tumour was not observed even after MLTC. These results do not exclude the existence of tumour-specific cytotoxic T lymphocytes in ovarian carcinoma; nevertheless they suggest that putative specific effectors have very low frequency and that culture techniques for expanding their growth more selectively are still to be optimized.